The murine I-A region gene products are cell surface antigens that may play a role in determining the immune response capabilities of the mouse. Considerable genetic and biochemical analyses of these polypeptides has already been performed. The I-A region gene products can be precipitated by alloantiserum and monoclonal antibodies. There are three chains associated with I-A--alpha, beta and invariant chain. Two of these chains, alpha (32,000 daltons) and beta (28,000 daltons) are polymorphic, while the invariant chain is not polymorphic among the inbred mouse strains. Since the alpha and beta chains are polymorphic they can be mapped genetically. Both of these chains are encoded in the major histocompatibility locus between H2-K and H2-D genes. We hope to better understand the organization of the genes that encode the alpha and beta chains. Unfortunately, the genes encoding these I-A polypeptides have not been amenable to recombinant DNA technologies. Because these cell surface antigens are made in very small amounts (less than 0.1% of the total cell protein) their mRNAs are rare, obtaining cDNA clones corresponding to these mRNAs has been difficult. Recently, we have developed a procedure for cloning a rare mRNA whose in vitro translation product can be detected (PNAs, April 1981). This procedure involves the rapid screening of large numbers of cDNA clones for their ability to select the desired mRNA. Furthermore, we have been able to detect the alpha and beta chains that are synthesized in Xenopus oocytes after injection of mRNA. Thus, we are confident that we will be able to clone the cDNAs for I-A alpha and beta chains. Using these cDNA probes we propose to identify and characterize the I-A genes. These studies should further our understanding of the mechanisms by which immune responses are regulated. Also, we should learn the basis for the extensive polymorphism of these genes.